Improved Methodology for the Preparation of Chiral Amines

superior in terms of conversion (89-92%) to the commercially applied Pt/C catalyst (74%
conversion) (scheme 3.5). [16]
O 10 bar H 2
PhHN NH2 PhHN NH
5h,120°C
[Rh(COD)(PPh 3 ) 2 ]BF 4 ,TON=1060
[Rh(COD)(PPh 3 ) 2 ]BF 4 on MM-K10, TON=1010
Scheme 3.5. Reductive Amination with Rhodium Supported Catalyst.
3.2. Reductive Amination the Current State of Art:
Reductive amination is a one-pot process in which the formation and the isolation of imines
or enamines are avoided. Over the last three decades several research groups studied this
transformation and factors affecting it. It was proved that pH has important influence on the
progress of the reaction. [17] It was proposed that reductive amination passes through reduction
of imine or iminium ion. As it is shown in (scheme 3.6), a carbonyl compound combines with
a primary or secondary amine to form a hemiaminal species which forms an iminium ion.
This iminium ion loses hydrogen resulting in the formation of imine which is then reduced to
the amine product. The most critical factor in reductive amination is the good choice of
conditions which favours intermediate reduction over ketone reduction to suppress alcohol
formation. [18]
O
R 1 R 2
H
N R 3
NH 2 R 3
HN R 3
H 2
R 1 R 2
R 1
HO
R 2
+H +
-H 2 O
H
N R 3
N R 4
+H 2 O
-H + R 1 R 2
R 1 R 2
Scheme 3.6. Mechanism of Reductive Amination.
The most common strategies in reductive amination representing the current state of art can
be subdivided into three main strategies. In the first strategy reduction is carried out using
molecular hydrogen with heterogeneous catalysts (palladium, platinum or nickel catalysts).
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